PK PD of the Enantiomers of Tramadol and O-desmethyltramadol in Elderly and Young Subjects

NCT02329561 | Completed Phase 1

• 1 other identifier: MDT1-20
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates the pharmacokinetics and pharmacodynamics of the enantiomers of tramadol and O-desmethyltramadol (ODM) in generally healthy young and elderly adults. Using a randomised, double-blind, crossover design, participants were administered a single 200mg tramadol extended-release tablet and placebo.

Conditions

Aging; Pain

Keywords

Pharmacokinetics; Opioid; Geriatric; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• To characterise and compare the pharmacokinetic parameters of AUC 0-t, AUCinf, Cmax, tmax, t½, CL/F, Varea/F, Ae 0 48, Rmax and CLr for the enantiomers of tramadol and O-desmethyltramadol in young and elderly subjects

  To characterise and compare the pharmacokinetic parameters of AUC 0-t, AUCinf, Cmax, tmax, t½, CL/F, Varea/F, Ae 0 48, Rmax and CLr for the enantiomers of tramadol and O-desmethyltramadol in healthy adult young and elderly subjects. Plasma samples were taken at 16 timepoints throughout 48 hours and evaluated for plasma concentrations of (+)- and (-)- tramadol

  48 hours

Secondary Outcomes (2)

• To characterise and compare threshold of current perception in young and elderly subjects

  30 hours

• To characterise and compare threshold of pain tolerance in young and elderly subjects

  30 hours

Study Arms (2)

Tramadol extended release and CP/T

ACTIVE COMPARATOR

Tramadol extended release: 200mg Single-dose, extended-release, once-daily, tablet; Current Perception and Tolerance (CP/T)

Drug: Tramadol extended release 200 mg; Behavioral: CP/T

Placebo and CP/T

PLACEBO COMPARATOR

Single-dose, placebo identical in appearance to an extended release once-daily tablet; Current Perception and Tolerance (CP/T)

Behavioral: CP/T; Drug: Placebo

Interventions

Tramadol extended release 200 mg DRUG

Tramadol extended release 200 mg: Administration of a single 200mg tramadol extended-release tablet

Also known as: Tramadol Contramid 200 mg extended-release

Tramadol extended release and CP/T

CP/T BEHAVIORAL

Subjects were evaluated for perception and tolerance of electrical current. An experimentally induced pain model utilizing electrical stimulation from the FDA approved Neurometer, as the painful stimulus was used to assess Current Perception Threshold and Pain Tolerance Threshold (CP/T) in young and elderly subjects following administration of tramadol and of placebo.

Also known as: Electrically stimulated experimental pain model (ESEPM)

Placebo and CP/T; Tramadol extended release and CP/T

Placebo DRUG

Administration of a single placebo tablet identical in appearance to a 200mg tramadol extended-release tablet

Also known as: sugar pill

Placebo and CP/T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adult male or female volunteers, 18-40 years of age.
• Adult male or female volunteers aged 75 years or more
• Subjects with a BMI less than 35 kg/m2.
• Generally healthy, elderly subjects with mild renal impairment (creatinine clearance 50-80 mL/min or glomerular filtration rate ≥ 50 mL/min/1.73 m2) or mild hepatic impairment (Child-Pugh Class A)
• Medically stable healthy subjects with non-clinically significant laboratory profiles, vital signs and ECGs.
• Subjects will be non-smokers for at least 3 months prior to the first dose or consistent moderate smokers (fewer than 10 cigarettes per day) for at least 3 months prior to the first dose.
• Females of childbearing potential must be using medically acceptable birth control methods
• Voluntary written informed consent

You may not qualify if:

• History or presence of significant unstable or untreated cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
• alcoholism or drug abuse within the past year;
• previous or current opioid dependency or other substance abuse or dependence, other than nicotine;
• hypersensitivity or idiosyncratic reaction to tramadol hydrochloride, codeine, opioids or other synthetic opioids of the aminocyclohexanol group;
• seizures (other than infantile febrile seizures);
• significant head trauma.
• Subjects who tested positive at screening for HIV, HBsAg or HCV.
• Subjects whose sitting blood pressure is less than 110/60 mmHg at screening or prior to dosing.
• Subjects whose pulse is lower than 55 b.p.m. at screening or prior to dosing for young subjects or less than 60 b.p.m at screening or prior to dosing for the elderly subjects.
• Subjects who have used any drugs or substances known to be strong inhibitors of CYP enzymes (formerly known as cytochrome P450 enzymes) within 10 days prior to the first dose.
• Subjects who have used any drugs or substances known to be strong inducers of CYP enzymes (formerly known as cytochrome P450 enzymes) within 28 days prior to the first dose.
• Subjects who are revealed upon genotyping to be CYP2D6 poor metabolisers.
• Subjects who have received monoamine oxidase inhibitors (MAOI) or antidepressants (tricyclic or SSRIs), within 28 days prior to the first dose.
• Subjects who have received drugs belonging to the opioids/analgesic class, within 5 elimination half-lives prior to the first dose.
• Subjects who have received coumarin derivatives (e.g warfarin) or digoxin, within 28 days prior to the first dose.

Sponsors & Collaborators

• Université de Montréal: lead
• Labopharm Inc.: collaborator
• MDS Pharma Services: collaborator

Related Publications (2)

• Robertson SS, Mouksassi MS, Varin F. Population Pharmacokinetic/Pharmacodynamic Modeling of O-Desmethyltramadol in Young and Elderly Healthy Volunteers. Drugs Aging. 2019 Aug;36(8):747-758. doi: 10.1007/s40266-019-00681-w.

  PMID: 31161580 DERIVED

• Skinner-Robertson S, Fradette C, Bouchard S, Mouksassi MS, Varin F. Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects. Drugs Aging. 2015 Dec;32(12):1029-43. doi: 10.1007/s40266-015-0315-4.

  PMID: 26508138 DERIVED

MeSH Terms

Conditions

Pain

Interventions

Sugars

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• France Varin, BPharm, PhD

  Université de Montréal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: France Varin B. Pharm. Ph.D, Full Professer

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: December 31, 2014
• Study Start: January 1, 2007
• Primary Completion: February 1, 2007
• Study Completion: February 1, 2007
• Last Updated: December 31, 2014

Record last verified: 2014-12